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Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.
10aAfrican Americans10aBody Mass Index10aCase-Control Studies10aGene Frequency10aGenetic Loci10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aLinkage Disequilibrium10aObesity10aPolymorphism, Single Nucleotide1 aMonda, Keri, L1 aChen, Gary, K1 aTaylor, Kira, C1 aPalmer, Cameron1 aEdwards, Todd, L1 aLange, Leslie, A1 aC Y Ng, Maggie1 aAdeyemo, Adebowale, A1 aAllison, Matthew, A1 aBielak, Lawrence, F1 aChen, Guanjie1 aGraff, Mariaelisa1 aIrvin, Marguerite, R1 aRhie, Suhn, K1 aLi, Guo1 aLiu, Yongmei1 aLiu, Youfang1 aLu, Yingchang1 aNalls, Michael, A1 aSun, Yan, V1 aWojczynski, Mary, K1 aYanek, Lisa, R1 aAldrich, Melinda, C1 aAdemola, Adeyinka1 aAmos, Christopher, I1 aBandera, Elisa, V1 aBock, Cathryn, H1 aBritton, Angela1 aBroeckel, Ulrich1 aCai, Quiyin1 aCaporaso, Neil, E1 aCarlson, Chris, S1 aCarpten, John1 aCasey, Graham1 aChen, Wei-Min1 aChen, Fang1 aChen, Yii-der, I1 aChiang, Charleston, W K1 aCoetzee, Gerhard, A1 aDemerath, Ellen1 aDeming-Halverson, Sandra, L1 aDriver, Ryan, W1 aDubbert, Patricia1 aFeitosa, Mary, F1 aFeng, Ye1 aFreedman, Barry, I1 aGillanders, Elizabeth, M1 aGottesman, Omri1 aGuo, Xiuqing1 aHaritunians, Talin1 aHarris, Tamara1 aHarris, Curtis, C1 aHennis, Anselm, J M1 aHernandez, Dena, G1 aMcNeill, Lorna, H1 aHoward, Timothy, D1 aHoward, Barbara, V1 aHoward, Virginia, J1 aJohnson, Karen, C1 aKang, Sun, J1 aKeating, Brendan, J1 aKolb, Suzanne1 aKuller, Lewis, H1 aKutlar, Abdullah1 aLangefeld, Carl, D1 aLettre, Guillaume1 aLohman, Kurt1 aLotay, Vaneet1 aLyon, Helen1 aManson, JoAnn, E1 aMaixner, William1 aMeng, Yan, A1 aMonroe, Kristine, R1 aMorhason-Bello, Imran1 aMurphy, Adam, B1 aMychaleckyj, Josyf, C1 aNadukuru, Raj1 aNathanson, Katherine, L1 aNayak, Uma1 aN'diaye, Amidou1 aNemesure, Barbara1 aWu, Suh-Yuh1 aLeske, Cristina1 aNeslund-Dudas, Christine1 aNeuhouser, Marian1 aNyante, Sarah1 aOchs-Balcom, Heather1 aOgunniyi, Adesola1 aOgundiran, Temidayo, O1 aOjengbede, Oladosu1 aOlopade, Olufunmilayo, I1 aPalmer, Julie, R1 aRuiz-Narvaez, Edward, A1 aPalmer, Nicholette, D1 aPress, Michael, F1 aRampersaud, Evandine1 aRasmussen-Torvik, Laura, J1 aRodriguez-Gil, Jorge, L1 aSalako, Babatunde1 aSchadt, Eric, E1 aSchwartz, Ann, G1 aShriner, Daniel, A1 aSiscovick, David1 aSmith, Shad, B1 aWassertheil-Smoller, Sylvia1 aSpeliotes, Elizabeth, K1 aSpitz, Margaret, R1 aSucheston, Lara1 aTaylor, Herman1 aTayo, Bamidele, O1 aTucker, Margaret, A1 aVan Den Berg, David, J1 aEdwards, Digna, R Velez1 aWang, Zhaoming1 aWiencke, John, K1 aWinkler, Thomas, W1 aWitte, John, S1 aWrensch, Margaret1 aWu, Xifeng1 aYang, James, J1 aLevin, Albert, M1 aYoung, Taylor, R1 aZakai, Neil, A1 aCushman, Mary1 aZanetti, Krista, A1 aZhao, Jing Hua1 aZhao, Wei1 aZheng, Yonglan1 aZhou, Jie1 aZiegler, Regina, G1 aZmuda, Joseph, M1 aFernandes, Jyotika, K1 aGilkeson, Gary, S1 aKamen, Diane, L1 aHunt, Kelly, J1 aSpruill, Ida, J1 aAmbrosone, Christine, B1 aAmbs, Stefan1 aArnett, Donna, K1 aAtwood, Larry1 aBecker, Diane, M1 aBerndt, Sonja, I1 aBernstein, Leslie1 aBlot, William, J1 aBorecki, Ingrid, B1 aBottinger, Erwin, P1 aBowden, Donald, W1 aBurke, Gregory1 aChanock, Stephen, J1 aCooper, Richard, S1 aDing, Jingzhong1 aDuggan, David1 aEvans, Michele, K1 aFox, Caroline1 aGarvey, Timothy1 aBradfield, Jonathan, P1 aHakonarson, Hakon1 aGrant, Struan, F A1 aHsing, Ann1 aChu, Lisa1 aHu, Jennifer, J1 aHuo, Dezheng1 aIngles, Sue, A1 aJohn, Esther, M1 aJordan, Joanne, M1 aKabagambe, Edmond, K1 aKardia, Sharon, L R1 aKittles, Rick, A1 aGoodman, Phyllis, J1 aKlein, Eric, A1 aKolonel, Laurence, N1 aLe Marchand, Loïc1 aLiu, Simin1 aMcKnight, Barbara1 aMillikan, Robert, C1 aMosley, Thomas, H1 aPadhukasahasram, Badri1 aWilliams, Keoki1 aPatel, Sanjay, R1 aPeters, Ulrike1 aPettaway, Curtis, A1 aPeyser, Patricia, A1 aPsaty, Bruce, M1 aRedline, Susan1 aRotimi, Charles, N1 aRybicki, Benjamin, A1 aSale, Michèle, M1 aSchreiner, Pamela, J1 aSignorello, Lisa, B1 aSingleton, Andrew, B1 aStanford, Janet, L1 aStrom, Sara, S1 aThun, Michael, J1 aVitolins, Mara1 aZheng, Wei1 aMoore, Jason, H1 aWilliams, Scott, M1 aKetkar, Shamika1 aZhu, Xiaofeng1 aZonderman, Alan, B1 aKooperberg, Charles1 aPapanicolaou, George, J1 aHenderson, Brian, E1 aReiner, Alex, P1 aHirschhorn, Joel, N1 aLoos, Ruth, J F1 aNorth, Kari, E1 aHaiman, Christopher, A1 aNABEC Consortium1 aUKBEC Consortium1 aBioBank Japan Project1 aAGEN Consortium uhttps://chs-nhlbi.org/node/607805814nas a2201345 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2014 eng d a1553-740400aMeta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.0 aMetaanalysis of genomewide association studies in African Americ c2014 Aug ae10045170 v103 aType 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)
10aAfrican Americans10aDiabetes Mellitus, Type 210aGenome-Wide Association Study10aHLA-B27 Antigen10aHMGA2 Protein10aHumans10aKCNQ1 Potassium Channel10aMutant Chimeric Proteins10aPolymorphism, Single Nucleotide10aTranscription Factor 7-Like 2 Protein1 aC Y Ng, Maggie1 aShriner, Daniel1 aChen, Brian, H1 aLi, Jiang1 aChen, Wei-Min1 aGuo, Xiuqing1 aLiu, Jiankang1 aBielinski, Suzette, J1 aYanek, Lisa, R1 aNalls, Michael, A1 aComeau, Mary, E1 aRasmussen-Torvik, Laura, J1 aJensen, Richard, A1 aEvans, Daniel, S1 aSun, Yan, V1 aAn, Ping1 aPatel, Sanjay, R1 aLu, Yingchang1 aLong, Jirong1 aArmstrong, Loren, L1 aWagenknecht, Lynne1 aYang, Lingyao1 aSnively, Beverly, M1 aPalmer, Nicholette, D1 aMudgal, Poorva1 aLangefeld, Carl, D1 aKeene, Keith, L1 aFreedman, Barry, I1 aMychaleckyj, Josyf, C1 aNayak, Uma1 aRaffel, Leslie, J1 aGoodarzi, Mark, O1 aChen, Y-D, Ida1 aTaylor, Herman, A1 aCorrea, Adolfo1 aSims, Mario1 aCouper, David1 aPankow, James, S1 aBoerwinkle, Eric1 aAdeyemo, Adebowale1 aDoumatey, Ayo1 aChen, Guanjie1 aMathias, Rasika, A1 aVaidya, Dhananjay1 aSingleton, Andrew, B1 aZonderman, Alan, B1 aIgo, Robert, P1 aSedor, John, R1 aKabagambe, Edmond, K1 aSiscovick, David, S1 aMcKnight, Barbara1 aRice, Kenneth1 aLiu, Yongmei1 aHsueh, Wen-Chi1 aZhao, Wei1 aBielak, Lawrence, F1 aKraja, Aldi1 aProvince, Michael, A1 aBottinger, Erwin, P1 aGottesman, Omri1 aCai, Qiuyin1 aZheng, Wei1 aBlot, William, J1 aLowe, William, L1 aPacheco, Jennifer, A1 aCrawford, Dana, C1 aGrundberg, Elin1 aRich, Stephen, S1 aHayes, Geoffrey1 aShu, Xiao-Ou1 aLoos, Ruth, J F1 aBorecki, Ingrid, B1 aPeyser, Patricia, A1 aCummings, Steven, R1 aPsaty, Bruce, M1 aFornage, Myriam1 aIyengar, Sudha, K1 aEvans, Michele, K1 aBecker, Diane, M1 aKao, Linda, W H1 aWilson, James, G1 aRotter, Jerome, I1 aSale, Michèle, M1 aLiu, Simin1 aRotimi, Charles, N1 aBowden, Donald, W1 aFIND Consortium1 aeMERGE Consortium1 aDIAGRAM Consortium1 aMuTHER Consortium1 aMEta-analysis of type 2 DIabetes in African Americans Consortium uhttps://chs-nhlbi.org/node/658505835nas a2201585 4500008004100000022001400041245012700055210006900182260001500251300001000266490000700276520141400283100001801697700002401715700001901739700002801758700001901786700001901805700002501824700001801849700001301867700002001880700002001900700002101920700001701941700002401958700002501982700001202007700002202019700002002041700002002061700002202081700002602103700001902129700001802148700001802166700002502184700002102209700002102230700002202251700002102273700001702294700001702311700001702328700001502345700002102360700002402381700003102405700002402436700002402460700002002484700001902504700001402523700002102537700002402558700001902582700002402601700002202625700001802647700001902665700002102684700002202705700001802727700002002745700002002765700002302785700001602808700002202824700002002846700001602866700002202882700002302904700002302927700001702950700002202967700002302989700001703012700002003029700002203049700002303071700001603094700002003110700001503130700002103145700002203166700001903188700002503207700002403232700002103256700002103277700002203298700001603320700002303336700002403359700002203383700001803405700001303423700001803436700002203454700002103476700002303497700002603520700002303546700002103569700002003590700002003610700002403630700001903654700002103673700002303694700002203717700002603739700002103765700002203786700002203808700002503830700002003855700002403875700002003899700002103919700002003940700001903960700002103979700002004000700002204020700002204042700002004064710002004084710002004104710002504124710002204149710002104171710002104192856003604213 2016 eng d a1537-660500aTrans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.0 aTransethnic Metaanalysis and Functional Annotation Illuminates t c2016 Jul 7 a56-750 v993 a
Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.
1 aLiu, Ching-Ti1 aRaghavan, Sridharan1 aMaruthur, Nisa1 aKabagambe, Edmond, Kato1 aHong, Jaeyoung1 aC Y Ng, Maggie1 aHivert, Marie-France1 aLu, Yingchang1 aAn, Ping1 aBentley, Amy, R1 aDrolet, Anne, M1 aGaulton, Kyle, J1 aGuo, Xiuqing1 aArmstrong, Loren, L1 aIrvin, Marguerite, R1 aLi, Man1 aLipovich, Leonard1 aRybin, Denis, V1 aTaylor, Kent, D1 aAgyemang, Charles1 aPalmer, Nicholette, D1 aCade, Brian, E1 aChen, Wei-Min1 aDauriz, Marco1 aDelaney, Joseph, A C1 aEdwards, Todd, L1 aEvans, Daniel, S1 aEvans, Michele, K1 aLange, Leslie, A1 aLeong, Aaron1 aLiu, Jingmin1 aLiu, Yongmei1 aNayak, Uma1 aPatel, Sanjay, R1 aPorneala, Bianca, C1 aRasmussen-Torvik, Laura, J1 aSnijder, Marieke, B1 aStallings, Sarah, C1 aTanaka, Toshiko1 aYanek, Lisa, R1 aZhao, Wei1 aBecker, Diane, M1 aBielak, Lawrence, F1 aBiggs, Mary, L1 aBottinger, Erwin, P1 aBowden, Donald, W1 aChen, Guanjie1 aCorrea, Adolfo1 aCouper, David, J1 aCrawford, Dana, C1 aCushman, Mary1 aEicher, John, D1 aFornage, Myriam1 aFranceschini, Nora1 aFu, Yi-Ping1 aGoodarzi, Mark, O1 aGottesman, Omri1 aHara, Kazuo1 aHarris, Tamara, B1 aJensen, Richard, A1 aJohnson, Andrew, D1 aJhun, Min, A1 aKarter, Andrew, J1 aKeller, Margaux, F1 aKho, Abel, N1 aKizer, Jorge, R1 aKrauss, Ronald, M1 aLangefeld, Carl, D1 aLi, Xiaohui1 aLiang, Jingling1 aLiu, Simin1 aLowe, William, L1 aMosley, Thomas, H1 aNorth, Kari, E1 aPacheco, Jennifer, A1 aPeyser, Patricia, A1 aPatrick, Alan, L1 aRice, Kenneth, M1 aSelvin, Elizabeth1 aSims, Mario1 aSmith, Jennifer, A1 aTajuddin, Salman, M1 aVaidya, Dhananjay1 aWren, Mary, P1 aYao, Jie1 aZhu, Xiaofeng1 aZiegler, Julie, T1 aZmuda, Joseph, M1 aZonderman, Alan, B1 aZwinderman, Aeilko, H1 aAdeyemo, Adebowale1 aBoerwinkle, Eric1 aFerrucci, Luigi1 aHayes, Geoffrey1 aKardia, Sharon, L R1 aMiljkovic, Iva1 aPankow, James, S1 aRotimi, Charles, N1 aSale, Michèle, M1 aWagenknecht, Lynne, E1 aArnett, Donna, K1 aChen, Yii-Der Ida1 aNalls, Michael, A1 aProvince, Michael, A1 aKao, Linda, W H1 aSiscovick, David, S1 aPsaty, Bruce, M1 aWilson, James, G1 aLoos, Ruth, J F1 aDupuis, Josée1 aRich, Stephen, S1 aFlorez, Jose, C1 aRotter, Jerome, I1 aMorris, Andrew, P1 aMeigs, James, B1 aAAAG Consortium1 aCARe Consortium1 aCOGENT-BP Consortium1 aeMERGE Consortium1 aMEDIA Consortium1 aMAGIC Consortium uhttps://chs-nhlbi.org/node/714106485nas a2201489 4500008004100000022001400041245020200055210006900257260001600326300001300342490000700355520221400362100001902576700002202595700001802617700002102635700001902656700001802675700001902693700001902712700002102731700002402752700001802776700002302794700001902817700002402836700001502860700001702875700002102892700002202913700002002935700002402955700002202979700002203001700002703023700001803050700001803068700002203086700002503108700002703133700002303160700001503183700002403198700002803222700002203250700002003272700002103292700002203313700002103335700002403356700001803380700002403398700002203422700002003444700002303464700002003487700002303507700002003530700002403550700001903574700001703593700001803610700001903628700002003647700001803667700001603685700001203701700002203713700001503735700002203750700002203772700001903794700002203813700001903835700002503854700002203879700002303901700001703924700002403941700002303965700002503988700001604013700001904029700002204048700001904070700001304089700001804102700002304120700002304143700002304166700001704189700001804206700002104224700002204245700002104267700002804288700001804316700001904334700001404353700001504367700002104382700002304403700002404426700002904450700001404479700002304493700002204516700002004538700002204558700002104580700002304601700002204624700002204646700002404668700001204692700002104704700002004725700002204745700002104767700002204788700002504810700002704835700002004862700001904882710005804901856003604959 2017 eng d a1553-740400aDiscovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African ancestry anthropometry genetics consortium.0 aDiscovery and finemapping of adiposity loci using high density i c2017 Apr 21 ae10067190 v133 aGenome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.
1 aC Y Ng, Maggie1 aGraff, Mariaelisa1 aLu, Yingchang1 aJustice, Anne, E1 aMudgal, Poorva1 aLiu, Ching-Ti1 aYoung, Kristin1 aYanek, Lisa, R1 aFeitosa, Mary, F1 aWojczynski, Mary, K1 aRand, Kristin1 aBrody, Jennifer, A1 aCade, Brian, E1 aDimitrov, Latchezar1 aDuan, Qing1 aGuo, Xiuqing1 aLange, Leslie, A1 aNalls, Michael, A1 aOkut, Hayrettin1 aTajuddin, Salman, M1 aTayo, Bamidele, O1 aVedantam, Sailaja1 aBradfield, Jonathan, P1 aChen, Guanjie1 aChen, Wei-Min1 aChesi, Alessandra1 aIrvin, Marguerite, R1 aPadhukasahasram, Badri1 aSmith, Jennifer, A1 aZheng, Wei1 aAllison, Matthew, A1 aAmbrosone, Christine, B1 aBandera, Elisa, V1 aBartz, Traci, M1 aBerndt, Sonja, I1 aBernstein, Leslie1 aBlot, William, J1 aBottinger, Erwin, P1 aCarpten, John1 aChanock, Stephen, J1 aChen, Yii-Der Ida1 aConti, David, V1 aCooper, Richard, S1 aFornage, Myriam1 aFreedman, Barry, I1 aGarcia, Melissa1 aGoodman, Phyllis, J1 aHsu, Yu-Han, H1 aHu, Jennifer1 aHuff, Chad, D1 aIngles, Sue, A1 aJohn, Esther, M1 aKittles, Rick1 aKlein, Eric1 aLi, Jin1 aMcKnight, Barbara1 aNayak, Uma1 aNemesure, Barbara1 aOgunniyi, Adesola1 aOlshan, Andrew1 aPress, Michael, F1 aRohde, Rebecca1 aRybicki, Benjamin, A1 aSalako, Babatunde1 aSanderson, Maureen1 aShao, Yaming1 aSiscovick, David, S1 aStanford, Janet, L1 aStevens, Victoria, L1 aStram, Alex1 aStrom, Sara, S1 aVaidya, Dhananjay1 aWitte, John, S1 aYao, Jie1 aZhu, Xiaofeng1 aZiegler, Regina, G1 aZonderman, Alan, B1 aAdeyemo, Adebowale1 aAmbs, Stefan1 aCushman, Mary1 aFaul, Jessica, D1 aHakonarson, Hakon1 aLevin, Albert, M1 aNathanson, Katherine, L1 aWare, Erin, B1 aWeir, David, R1 aZhao, Wei1 aZhi, Degui1 aArnett, Donna, K1 aGrant, Struan, F A1 aKardia, Sharon, L R1 aOloapde, Olufunmilayo, I1 aRao, D, C1 aRotimi, Charles, N1 aSale, Michèle, M1 aWilliams, Keoki1 aZemel, Babette, S1 aBecker, Diane, M1 aBorecki, Ingrid, B1 aEvans, Michele, K1 aHarris, Tamara, B1 aHirschhorn, Joel, N1 aLi, Yun1 aPatel, Sanjay, R1 aPsaty, Bruce, M1 aRotter, Jerome, I1 aWilson, James, G1 aBowden, Donald, W1 aCupples, Adrienne, L1 aHaiman, Christopher, A1 aLoos, Ruth, J F1 aNorth, Kari, E1 aBone Mineral Density in Childhood Study (BMDCS) Group uhttps://chs-nhlbi.org/node/735204450nas a2201069 4500008004100000022001400041245015100055210006900206260001300275300001200288490000700300520139200307100002101699700001901720700002301739700002301762700001601785700002001801700001901821700002101840700002501861700002301886700002101909700001801930700002201948700001701970700002701987700002202014700001702036700002102053700002002074700002002094700001502114700001402129700001702143700001602160700001702176700001702193700002102210700001702231700001302248700002002261700002102281700001902302700002302321700001402344700002102358700001902379700002302398700001802421700001802439700003202457700002702489700001702516700002202533700001602555700001902571700002302590700002102613700001902634700002102653700002202674700001802696700002002714700002202734700001702756700002002773700001702793700001902810700002102829700001902850700002002869700001902889700002402908700002302932700001802955700002202973700002102995700002103016700002503037700001903062700002303081700001803104700002403122700001803146700002203164700002203186700002003208700001803228710009803246856003603344 2019 eng d a1939-327X00aMultiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control.0 aMultiethnic GenomeWide Association Study of Diabetic Retinopathy c2019 Feb a441-4560 v683 aTo identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts ( = 3,246) and seven African American cohorts ( = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a value <1 × 10 were investigated in replication cohorts that included 18,545 European, 16,453 Asian, and 2,710 Hispanic subjects. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like () was associated with DR in European discovery cohorts ( = 2.1 × 10), but did not reach genome-wide significance after meta-analysis with replication cohorts. We applied the Disease Association Protein-Protein Link Evaluator (DAPPLE) to our discovery results to test for evidence of risk being spread across underlying molecular pathways. One protein-protein interaction network built from genes in regions associated with proliferative DR was found to have significant connectivity ( = 0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in as well as variation within a protein-protein interaction network that includes genes implicated in inflammation, may influence risk for DR.
1 aPollack, Samuela1 aIgo, Robert, P1 aJensen, Richard, A1 aChristiansen, Mark1 aLi, Xiaohui1 aCheng, Ching-Yu1 aC Y Ng, Maggie1 aSmith, Albert, V1 aRossin, Elizabeth, J1 aSegrè, Ayellet, V1 aDavoudi, Samaneh1 aTan, Gavin, S1 aChen, Yii-Der Ida1 aKuo, Jane, Z1 aDimitrov, Latchezar, M1 aStanwyck, Lynn, K1 aMeng, Weihua1 aHosseini, Mohsen1 aImamura, Minako1 aNousome, Darryl1 aKim, Jihye1 aHai, Yang1 aJia, Yucheng1 aAhn, Jeeyun1 aLeong, Aaron1 aShah, Kaanan1 aPark, Kyu, Hyung1 aGuo, Xiuqing1 aIpp, Eli1 aTaylor, Kent, D1 aAdler, Sharon, G1 aSedor, John, R1 aFreedman, Barry, I1 aLee, I-Te1 aSheu, Wayne, H-H1 aKubo, Michiaki1 aTakahashi, Atsushi1 aHadjadj, Samy1 aMarre, Michel1 aTrégouët, David-Alexandre1 aMcKean-Cowdin, Roberta1 aVarma, Rohit1 aMcCarthy, Mark, I1 aGroop, Leif1 aAhlqvist, Emma1 aLyssenko, Valeriya1 aAgardh, Elisabet1 aMorris, Andrew1 aDoney, Alex, S F1 aColhoun, Helen, M1 aToppila, Iiro1 aSandholm, Niina1 aGroop, Per-Henrik1 aMaeda, Shiro1 aHanis, Craig, L1 aPenman, Alan1 aChen, Ching, J1 aHancock, Heather1 aMitchell, Paul1 aCraig, Jamie, E1 aChew, Emily, Y1 aPaterson, Andrew, D1 aGrassi, Michael, A1 aPalmer, Colin1 aBowden, Donald, W1 aYaspan, Brian, L1 aSiscovick, David1 aCotch, Mary, Frances1 aWang, Jie, Jin1 aBurdon, Kathryn, P1 aWong, Tien, Y1 aKlein, Barbara, E K1 aKlein, Ronald1 aRotter, Jerome, I1 aIyengar, Sudha, K1 aPrice, Alkes, L1 aSobrin, Lucia1 aFamily Investigation of Nephropathy and Diabetes-Eye Research Group, DCCT/EDIC Research Group uhttps://chs-nhlbi.org/node/799006377nas a2201849 4500008004100000022001400041245011300055210006900168260001500237300000900252490000700261520114200268653001001410653003701420653001501457653003001472653001801502653001001520653003801530653001301568653001101581653003101592653001501623653002001638100002301658700002401681700001601705700002001721700001701741700002001758700002001778700001801798700001601816700001901832700001901851700002001870700002101890700001901911700002401930700001501954700003101969700001602000700002902016700001802045700001902063700002102082700002502103700002102128700002202149700002702171700002202198700002002220700001702240700001802257700002002275700001902295700002902314700002102343700001902364700002302383700002802406700001902434700003102453700002802484700002202512700002102534700003602555700002402591700001802615700001602633700001702649700002402666700001502690700002002705700001902725700002602744700002402770700003202794700002102826700002602847700002502873700002002898700001702918700002002935700002502955700002602980700002203006700001903028700001903047700001803066700002003084700001703104700002103121700002103142700001703163700002003180700002303200700002003223700003603243700002003279700002203299700002603321700002103347700002203368700002403390700001903414700002203433700003003455700001903485700002303504700002103527700001903548700001903567700002003586700002003606700002503626700003103651700002103682700002203703700002103725700002303746700001703769700001603786700002103802700001803823700002403841700002403865700001803889700001903907700002203926700001903948700002003967700002103987700002204008700002204030700002304052700002404075700002004099700002704119700002104146700002104167700001904188700001904207700001804226700002204244700002104266700002004287700002004307700002304327700002604350700002104376700002004397700002504417700002104442710002804463856003604491 2021 eng d a2041-172300aDeterminants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.0 aDeterminants of penetrance and variable expressivity in monogeni c2021 06 09 a35050 v123 aHundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.
10aAdult10aBiological Variation, Population10aBiomarkers10aDiabetes Mellitus, Type 210aDyslipidemias10aExome10aGenetic Predisposition to Disease10aGenotype10aHumans10aMultifactorial Inheritance10aPenetrance10aRisk Assessment1 aGoodrich, Julia, K1 aSinger-Berk, Moriel1 aSon, Rachel1 aSveden, Abigail1 aWood, Jordan1 aEngland, Eleina1 aCole, Joanne, B1 aWeisburd, Ben1 aWatts, Nick1 aCaulkins, Lizz1 aDornbos, Peter1 aKoesterer, Ryan1 aZappala, Zachary1 aZhang, Haichen1 aMaloney, Kristin, A1 aDahl, Andy1 aAguilar-Salinas, Carlos, A1 aAtzmon, Gil1 aBarajas-Olmos, Francisco1 aBarzilai, Nir1 aBlangero, John1 aBoerwinkle, Eric1 aBonnycastle, Lori, L1 aBottinger, Erwin1 aBowden, Donald, W1 aCenteno-Cruz, Federico1 aChambers, John, C1 aChami, Nathalie1 aChan, Edmund1 aChan, Juliana1 aCheng, Ching-Yu1 aCho, Yoon Shin1 aContreras-Cubas, Cecilia1 aCórdova, Emilio1 aCorrea, Adolfo1 aDeFronzo, Ralph, A1 aDuggirala, Ravindranath1 aDupuis, Josée1 aGaray-Sevilla, Ma, Eugenia1 aGarcía-Ortiz, Humberto1 aGieger, Christian1 aGlaser, Benjamin1 aGonzález-Villalpando, Clicerio1 aGonzalez, Ma, Elena1 aGrarup, Niels1 aGroop, Leif1 aGross, Myron1 aHaiman, Christopher1 aHan, Sohee1 aHanis, Craig, L1 aHansen, Torben1 aHeard-Costa, Nancy, L1 aHenderson, Brian, E1 aHernandez, Juan, Manuel Mal1 aHwang, Mi, Yeong1 aIslas-Andrade, Sergio1 aJørgensen, Marit, E1 aKang, Hyun, Min1 aKim, Bong-Jo1 aKim, Young, Jin1 aKoistinen, Heikki, A1 aKooner, Jaspal, Singh1 aKuusisto, Johanna1 aKwak, Soo-Heon1 aLaakso, Markku1 aLange, Leslie1 aLee, Jong-Young1 aLee, Juyoung1 aLehman, Donna, M1 aLinneberg, Allan1 aLiu, Jianjun1 aLoos, Ruth, J F1 aLyssenko, Valeriya1 aMa, Ronald, C W1 aMartínez-Hernández, Angélica1 aMeigs, James, B1 aMeitinger, Thomas1 aMendoza-Caamal, Elvia1 aMohlke, Karen, L1 aMorris, Andrew, D1 aMorrison, Alanna, C1 aC Y Ng, Maggie1 aNilsson, Peter, M1 aO'Donnell, Christopher, J1 aOrozco, Lorena1 aPalmer, Colin, N A1 aPark, Kyong, Soo1 aPost, Wendy, S1 aPedersen, Oluf1 aPreuss, Michael1 aPsaty, Bruce, M1 aReiner, Alexander, P1 aRevilla-Monsalve, Cristina1 aRich, Stephen, S1 aRotter, Jerome, I1 aSaleheen, Danish1 aSchurmann, Claudia1 aSim, Xueling1 aSladek, Rob1 aSmall, Kerrin, S1 aSo, Wing, Yee1 aSpector, Timothy, D1 aStrauch, Konstantin1 aStrom, Tim, M1 aTai, Shyong, E1 aTam, Claudia, H T1 aTeo, Yik, Ying1 aThameem, Farook1 aTomlinson, Brian1 aTracy, Russell, P1 aTuomi, Tiinamaija1 aTuomilehto, Jaakko1 aTusié-Luna, Teresa1 avan Dam, Rob, M1 aVasan, Ramachandran, S1 aWilson, James, G1 aWitte, Daniel, R1 aWong, Tien-Yin1 aBurtt, Noel, P1 aZaitlen, Noah1 aMcCarthy, Mark, I1 aBoehnke, Michael1 aPollin, Toni, I1 aFlannick, Jason1 aMercader, Josep, M1 aO'Donnell-Luria, Anne1 aBaxter, Samantha1 aFlorez, Jose, C1 aMacArthur, Daniel, G1 aUdler, Miriam, S1 aAMP-T2D-GENES Consortia uhttps://chs-nhlbi.org/node/877409591nas a2202833 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2021 eng d a1537-660500aDiscovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.0 aDiscovery and finemapping of height loci via highdensity imputat c2021 Apr 01 a564-5820 v1083 aAlthough many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
1 aGraff, Mariaelisa1 aJustice, Anne, E1 aYoung, Kristin, L1 aMarouli, Eirini1 aZhang, Xinruo1 aFine, Rebecca, S1 aLim, Elise1 aBuchanan, Victoria1 aRand, Kristin1 aFeitosa, Mary, F1 aWojczynski, Mary, K1 aYanek, Lisa, R1 aShao, Yaming1 aRohde, Rebecca1 aAdeyemo, Adebowale, A1 aAldrich, Melinda, C1 aAllison, Matthew, A1 aAmbrosone, Christine, B1 aAmbs, Stefan1 aAmos, Christopher1 aArnett, Donna, K1 aAtwood, Larry1 aBandera, Elisa, V1 aBartz, Traci1 aBecker, Diane, M1 aBerndt, Sonja, I1 aBernstein, Leslie1 aBielak, Lawrence, F1 aBlot, William, J1 aBottinger, Erwin, P1 aBowden, Donald, W1 aBradfield, Jonathan, P1 aBrody, Jennifer, A1 aBroeckel, Ulrich1 aBurke, Gregory1 aCade, Brian, E1 aCai, Qiuyin1 aCaporaso, Neil1 aCarlson, Chris1 aCarpten, John1 aCasey, Graham1 aChanock, Stephen, J1 aChen, Guanjie1 aChen, Minhui1 aChen, Yii-der, I1 aChen, Wei-Min1 aChesi, Alessandra1 aChiang, Charleston, W K1 aChu, Lisa1 aCoetzee, Gerry, A1 aConti, David, V1 aCooper, Richard, S1 aCushman, Mary1 aDemerath, Ellen1 aDeming, Sandra, L1 aDimitrov, Latchezar1 aDing, Jingzhong1 aDiver, Ryan1 aDuan, Qing1 aEvans, Michele, K1 aFalusi, Adeyinka, G1 aFaul, Jessica, D1 aFornage, Myriam1 aFox, Caroline1 aFreedman, Barry, I1 aGarcia, Melissa1 aGillanders, Elizabeth, M1 aGoodman, Phyllis1 aGottesman, Omri1 aGrant, Struan, F A1 aGuo, Xiuqing1 aHakonarson, Hakon1 aHaritunians, Talin1 aHarris, Tamara, B1 aHarris, Curtis, C1 aHenderson, Brian, E1 aHennis, Anselm1 aHernandez, Dena, G1 aHirschhorn, Joel, N1 aMcNeill, Lorna, Haughton1 aHoward, Timothy, D1 aHoward, Barbara1 aHsing, Ann, W1 aHsu, Yu-Han, H1 aHu, Jennifer, J1 aHuff, Chad, D1 aHuo, Dezheng1 aIngles, Sue, A1 aIrvin, Marguerite, R1 aJohn, Esther, M1 aJohnson, Karen, C1 aJordan, Joanne, M1 aKabagambe, Edmond, K1 aKang, Sun, J1 aKardia, Sharon, L1 aKeating, Brendan, J1 aKittles, Rick, A1 aKlein, Eric, A1 aKolb, Suzanne1 aKolonel, Laurence, N1 aKooperberg, Charles1 aKuller, Lewis1 aKutlar, Abdullah1 aLange, Leslie1 aLangefeld, Carl, D1 aLe Marchand, Loïc1 aLeonard, Hampton1 aLettre, Guillaume1 aLevin, Albert, M1 aLi, Yun1 aLi, Jin1 aLiu, Yongmei1 aLiu, Youfang1 aLiu, Simin1 aLohman, Kurt1 aLotay, Vaneet1 aLu, Yingchang1 aMaixner, William1 aManson, JoAnn, E1 aMcKnight, Barbara1 aMeng, Yan1 aMonda, Keri, L1 aMonroe, Kris1 aMoore, Jason, H1 aMosley, Thomas, H1 aMudgal, Poorva1 aMurphy, Adam, B1 aNadukuru, Raj1 aNalls, Mike, A1 aNathanson, Katherine, L1 aNayak, Uma1 aN'diaye, Amidou1 aNemesure, Barbara1 aNeslund-Dudas, Christine1 aNeuhouser, Marian, L1 aNyante, Sarah1 aOchs-Balcom, Heather1 aOgundiran, Temidayo, O1 aOgunniyi, Adesola1 aOjengbede, Oladosu1 aOkut, Hayrettin1 aOlopade, Olufunmilayo, I1 aOlshan, Andrew1 aPadhukasahasram, Badri1 aPalmer, Julie1 aPalmer, Cameron, D1 aPalmer, Nicholette, D1 aPapanicolaou, George1 aPatel, Sanjay, R1 aPettaway, Curtis, A1 aPeyser, Patricia, A1 aPress, Michael, F1 aRao, D, C1 aRasmussen-Torvik, Laura, J1 aRedline, Susan1 aReiner, Alex, P1 aRhie, Suhn, K1 aRodriguez-Gil, Jorge, L1 aRotimi, Charles, N1 aRotter, Jerome, I1 aRuiz-Narvaez, Edward, A1 aRybicki, Benjamin, A1 aSalako, Babatunde1 aSale, Michèle, M1 aSanderson, Maureen1 aSchadt, Eric1 aSchreiner, Pamela, J1 aSchurmann, Claudia1 aSchwartz, Ann, G1 aShriner, Daniel, A1 aSignorello, Lisa, B1 aSingleton, Andrew, B1 aSiscovick, David, S1 aSmith, Jennifer, A1 aSmith, Shad1 aSpeliotes, Elizabeth1 aSpitz, Margaret1 aStanford, Janet, L1 aStevens, Victoria, L1 aStram, Alex1 aStrom, Sara, S1 aSucheston, Lara1 aSun, Yan, V1 aTajuddin, Salman, M1 aTaylor, Herman1 aTaylor, Kira1 aTayo, Bamidele, O1 aThun, Michael, J1 aTucker, Margaret, A1 aVaidya, Dhananjay1 aVan Den Berg, David, J1 aVedantam, Sailaja1 aVitolins, Mara1 aWang, Zhaoming1 aWare, Erin, B1 aWassertheil-Smoller, Sylvia1 aWeir, David, R1 aWiencke, John, K1 aWilliams, Scott, M1 aWilliams, Keoki1 aWilson, James, G1 aWitte, John, S1 aWrensch, Margaret1 aWu, Xifeng1 aYao, Jie1 aZakai, Neil1 aZanetti, Krista1 aZemel, Babette, S1 aZhao, Wei1 aZhao, Jing Hua1 aZheng, Wei1 aZhi, Degui1 aZhou, Jie1 aZhu, Xiaofeng1 aZiegler, Regina, G1 aZmuda, Joe1 aZonderman, Alan, B1 aPsaty, Bruce, M1 aBorecki, Ingrid, B1 aCupples, Adrienne, L1 aLiu, Ching-Ti1 aHaiman, Christopher, A1 aLoos, Ruth1 aC Y Ng, Maggie1 aNorth, Kari, E uhttps://chs-nhlbi.org/node/870503781nas a2200637 4500008004100000022001400041245011400055210006900169260001300238300001200251490000700263520196300270100001802233700002402251700002002275700002402295700001902319700002102338700001502359700002002374700002302394700002102417700001602438700001802454700001302472700001502485700002602500700002802526700001602554700002102570700002002591700002002611700002002631700002302651700002302674700003002697700001302727700002302740700002302763700001602786700001702802700001902819700002402838700002102862700002302883700001802906700002802924700002102952700002402973700002702997700002003024700002203044700002203066700001903088856003603107 2021 eng d a2574-830000aMultiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes.0 aMultiethnic GenomeWide Association Study of Subclinical Atherosc c2021 Aug ae0032580 v143 aBACKGROUND: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.
METHODS: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.
RESULTS: We replicated 2 loci (rs9369640 and rs9349379 near and rs10757278 near ) for CAC and one locus for cIMT (rs7412 and rs445925 near ) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near at 13q13.3) at =2.0×10 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints , encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (<3.1×10) for 3 previously reported coronary artery disease loci for these subclinical atherosclerotic phenotypes (rs2891168 near and rs11170820 near for CAC, and rs7412 near for cIMT).
CONCLUSIONS: Our results provide potential biological mechanisms that could link CAC and cIMT to increased cardiovascular disease risk in individuals with T2D.
1 aLu, Yingchang1 aDimitrov, Latchezar1 aChen, Shyh-Huei1 aBielak, Lawrence, F1 aBis, Joshua, C1 aFeitosa, Mary, F1 aLu, Lingyi1 aKavousi, Maryam1 aRaffield, Laura, M1 aSmith, Albert, V1 aWang, Lihua1 aWeiss, Stefan1 aYao, Jie1 aZhu, Jiaxi1 aGudmundsson, Elias, F1 aGudmundsdottir, Valborg1 aBos, Daniel1 aGhanbari, Mohsen1 aIkram, Arfan, M1 aHwang, Shih-Jen1 aTaylor, Kent, D1 aBudoff, Matthew, J1 aGislason, Gauti, K1 aO'Donnell, Christopher, J1 aAn, Ping1 aFranceschini, Nora1 aFreedman, Barry, I1 aFu, Yi-Ping1 aGuo, Xiuqing1 aHeiss, Gerardo1 aKardia, Sharon, L R1 aWilson, James, G1 aLangefeld, Carl, D1 aSchminke, Ulf1 aUitterlinden, André, G1 aLange, Leslie, A1 aPeyser, Patricia, A1 aGudnason, Vilmundur, G1 aPsaty, Bruce, M1 aRotter, Jerome, I1 aBowden, Donald, W1 aC Y Ng, Maggie uhttps://chs-nhlbi.org/node/883213363nas a2204429 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2022 eng d a1546-171800aMulti-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.0 aMultiancestry genetic study of type 2 diabetes highlights the po c2022 May a560-5720 v543 aWe assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.
10aDiabetes Mellitus, Type 210aEthnicity10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aPolymorphism, Single Nucleotide10aRisk Factors1 aMahajan, Anubha1 aSpracklen, Cassandra, N1 aZhang, Weihua1 aC Y Ng, Maggie1 aPetty, Lauren, E1 aKitajima, Hidetoshi1 aYu, Grace, Z1 aRüeger, Sina1 aSpeidel, Leo1 aKim, Young, Jin1 aHorikoshi, Momoko1 aMercader, Josep, M1 aTaliun, Daniel1 aMoon, Sanghoon1 aKwak, Soo-Heon1 aRobertson, Neil, R1 aRayner, Nigel, W1 aLoh, Marie1 aKim, Bong-Jo1 aChiou, Joshua1 aMiguel-Escalada, Irene1 aParolo, Pietro, Della Brio1 aLin, Kuang1 aBragg, Fiona1 aPreuss, Michael, H1 aTakeuchi, Fumihiko1 aNano, Jana1 aGuo, Xiuqing1 aLamri, Amel1 aNakatochi, Masahiro1 aScott, Robert, A1 aLee, Jung-Jin1 aHuerta-Chagoya, Alicia1 aGraff, Mariaelisa1 aChai, Jin-Fang1 aParra, Esteban, J1 aYao, Jie1 aBielak, Lawrence, F1 aTabara, Yasuharu1 aHai, Yang1 aSteinthorsdottir, Valgerdur1 aCook, James, P1 aKals, Mart1 aGrarup, Niels1 aSchmidt, Ellen, M1 aPan, Ian1 aSofer, Tamar1 aWuttke, Matthias1 aSarnowski, Chloe1 aGieger, Christian1 aNousome, Darryl1 aTrompet, Stella1 aLong, Jirong1 aSun, Meng1 aTong, Lin1 aChen, Wei-Min1 aAhmad, Meraj1 aNoordam, Raymond1 aJ Y Lim, Victor1 aTam, Claudia, H T1 aJoo, Yoonjung, Yoonie1 aChen, Chien-Hsiun1 aRaffield, Laura, M1 aLecoeur, Cécile1 aPrins, Bram, Peter1 aNicolas, Aude1 aYanek, Lisa, R1 aChen, Guanjie1 aJensen, Richard, A1 aTajuddin, Salman1 aKabagambe, Edmond, K1 aAn, Ping1 aXiang, Anny, H1 aChoi, Hyeok, Sun1 aCade, Brian, E1 aTan, Jingyi1 aFlanagan, Jack1 aAbaitua, Fernando1 aAdair, Linda, S1 aAdeyemo, Adebowale1 aAguilar-Salinas, Carlos, A1 aAkiyama, Masato1 aAnand, Sonia, S1 aBertoni, Alain1 aBian, Zheng1 aBork-Jensen, Jette1 aBrandslund, Ivan1 aBrody, Jennifer, A1 aBrummett, Chad, M1 aBuchanan, Thomas, A1 aCanouil, Mickaël1 aChan, Juliana, C N1 aChang, Li-Ching1 aChee, Miao-Li1 aChen, Ji1 aChen, Shyh-Huei1 aChen, Yuan-Tsong1 aChen, Zhengming1 aChuang, Lee-Ming1 aCushman, Mary1 aDas, Swapan, K1 ade Silva, Janaka1 aDedoussis, George1 aDimitrov, Latchezar1 aDoumatey, Ayo, P1 aDu, Shufa1 aDuan, Qing1 aEckardt, Kai-Uwe1 aEmery, Leslie, S1 aEvans, Daniel, S1 aEvans, Michele, K1 aFischer, Krista1 aFloyd, James, S1 aFord, Ian1 aFornage, Myriam1 aFranco, Oscar, H1 aFrayling, Timothy, M1 aFreedman, Barry, I1 aFuchsberger, Christian1 aGenter, Pauline1 aGerstein, Hertzel, C1 aGiedraitis, Vilmantas1 aGonzález-Villalpando, Clicerio1 aGonzalez-Villalpando, Maria, Elena1 aGoodarzi, Mark, O1 aGordon-Larsen, Penny1 aGorkin, David1 aGross, Myron1 aGuo, Yu1 aHackinger, Sophie1 aHan, Sohee1 aHattersley, Andrew, T1 aHerder, Christian1 aHoward, Annie-Green1 aHsueh, Willa1 aHuang, Mengna1 aHuang, Wei1 aHung, Yi-Jen1 aHwang, Mi, Yeong1 aHwu, Chii-Min1 aIchihara, Sahoko1 aIkram, Mohammad, Arfan1 aIngelsson, Martin1 aIslam, Md, Tariqul1 aIsono, Masato1 aJang, Hye-Mi1 aJasmine, Farzana1 aJiang, Guozhi1 aJonas, Jost, B1 aJørgensen, Marit, E1 aJørgensen, Torben1 aKamatani, Yoichiro1 aKandeel, Fouad, R1 aKasturiratne, Anuradhani1 aKatsuya, Tomohiro1 aKaur, Varinderpal1 aKawaguchi, Takahisa1 aKeaton, Jacob, M1 aKho, Abel, N1 aKhor, Chiea-Chuen1 aKibriya, Muhammad, G1 aKim, Duk-Hwan1 aKohara, Katsuhiko1 aKriebel, Jennifer1 aKronenberg, Florian1 aKuusisto, Johanna1 aLäll, Kristi1 aLange, Leslie, A1 aLee, Myung-Shik1 aLee, Nanette, R1 aLeong, Aaron1 aLi, Liming1 aLi, Yun1 aLi-Gao, Ruifang1 aLigthart, Symen1 aLindgren, Cecilia, M1 aLinneberg, Allan1 aLiu, Ching-Ti1 aLiu, Jianjun1 aLocke, Adam, E1 aLouie, Tin1 aLuan, Jian'an1 aLuk, Andrea, O1 aLuo, Xi1 aLv, Jun1 aLyssenko, Valeriya1 aMamakou, Vasiliki1 aMani, Radha, K1 aMeitinger, Thomas1 aMetspalu, Andres1 aMorris, Andrew, D1 aNadkarni, Girish, N1 aNadler, Jerry, L1 aNalls, Michael, A1 aNayak, Uma1 aNongmaithem, Suraj, S1 aNtalla, Ioanna1 aOkada, Yukinori1 aOrozco, Lorena1 aPatel, Sanjay, R1 aPereira, Mark, A1 aPeters, Annette1 aPirie, Fraser, J1 aPorneala, Bianca1 aPrasad, Gauri1 aPreissl, Sebastian1 aRasmussen-Torvik, Laura, J1 aReiner, Alexander, P1 aRoden, Michael1 aRohde, Rebecca1 aRoll, Kathryn1 aSabanayagam, Charumathi1 aSander, Maike1 aSandow, Kevin1 aSattar, Naveed1 aSchönherr, Sebastian1 aSchurmann, Claudia1 aShahriar, Mohammad1 aShi, Jinxiu1 aShin, Dong, Mun1 aShriner, Daniel1 aSmith, Jennifer, A1 aSo, Wing, Yee1 aStančáková, Alena1 aStilp, Adrienne, M1 aStrauch, Konstantin1 aSuzuki, Ken1 aTakahashi, Atsushi1 aTaylor, Kent, D1 aThorand, Barbara1 aThorleifsson, Gudmar1 aThorsteinsdottir, Unnur1 aTomlinson, Brian1 aTorres, Jason, M1 aTsai, Fuu-Jen1 aTuomilehto, Jaakko1 aTusié-Luna, Teresa1 aUdler, Miriam, S1 aValladares-Salgado, Adan1 avan Dam, Rob, M1 avan Klinken, Jan, B1 aVarma, Rohit1 aVujkovic, Marijana1 aWacher-Rodarte, Niels1 aWheeler, Eleanor1 aWhitsel, Eric, A1 aWickremasinghe, Ananda, R1 aDijk, Ko Willems1 aWitte, Daniel, R1 aYajnik, Chittaranjan, S1 aYamamoto, Ken1 aYamauchi, Toshimasa1 aYengo, Loic1 aYoon, Kyungheon1 aYu, Canqing1 aYuan, Jian-Min1 aYusuf, Salim1 aZhang, Liang1 aZheng, Wei1 aRaffel, Leslie, J1 aIgase, Michiya1 aIpp, Eli1 aRedline, Susan1 aCho, Yoon Shin1 aLind, Lars1 aProvince, Michael, A1 aHanis, Craig, L1 aPeyser, Patricia, A1 aIngelsson, Erik1 aZonderman, Alan, B1 aPsaty, Bruce, M1 aWang, Ya-Xing1 aRotimi, Charles, N1 aBecker, Diane, M1 aMatsuda, Fumihiko1 aLiu, Yongmei1 aZeggini, Eleftheria1 aYokota, Mitsuhiro1 aRich, Stephen, S1 aKooperberg, Charles1 aPankow, James, S1 aEngert, James, C1 aChen, Yii-Der Ida1 aFroguel, Philippe1 aWilson, James, G1 aSheu, Wayne, H H1 aKardia, Sharon, L R1 aWu, Jer-Yuarn1 aHayes, Geoffrey1 aMa, Ronald, C W1 aWong, Tien-Yin1 aGroop, Leif1 aMook-Kanamori, Dennis, O1 aChandak, Giriraj, R1 aCollins, Francis, S1 aBharadwaj, Dwaipayan1 aParé, Guillaume1 aSale, Michèle, M1 aAhsan, Habibul1 aMotala, Ayesha, A1 aShu, Xiao-Ou1 aPark, Kyong-Soo1 aJukema, Wouter1 aCruz, Miguel1 aMcKean-Cowdin, Roberta1 aGrallert, Harald1 aCheng, Ching-Yu1 aBottinger, Erwin, P1 aDehghan, Abbas1 aTai, E-Shyong1 aDupuis, Josée1 aKato, Norihiro1 aLaakso, Markku1 aKöttgen, Anna1 aKoh, Woon-Puay1 aPalmer, Colin, N A1 aLiu, Simin1 aAbecasis, Goncalo1 aKooner, Jaspal, S1 aLoos, Ruth, J F1 aNorth, Kari, E1 aHaiman, Christopher, A1 aFlorez, Jose, C1 aSaleheen, Danish1 aHansen, Torben1 aPedersen, Oluf1 aMägi, Reedik1 aLangenberg, Claudia1 aWareham, Nicholas, J1 aMaeda, Shiro1 aKadowaki, Takashi1 aLee, Juyoung1 aMillwood, Iona, Y1 aWalters, Robin, G1 aStefansson, Kari1 aMyers, Simon, R1 aFerrer, Jorge1 aGaulton, Kyle, J1 aMeigs, James, B1 aMohlke, Karen, L1 aGloyn, Anna, L1 aBowden, Donald, W1 aBelow, Jennifer, E1 aChambers, John, C1 aSim, Xueling1 aBoehnke, Michael1 aRotter, Jerome, I1 aMcCarthy, Mark, I1 aMorris, Andrew, P1 aFinnGen1 aeMERGE Consortium uhttps://chs-nhlbi.org/node/910413865nas a2204393 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2023 eng d00aMulti-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.0 aMultiancestry genomewide study in 25 million individuals reveals c2023 Mar 313 aType 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases. We identify 1,289 independent association signals at genome-wide significance (P<5×10 ) that map to 611 loci, of which 145 loci are previously unreported. We define eight non-overlapping clusters of T2D signals characterised by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial, and enteroendocrine cells. We build cluster-specific partitioned genetic risk scores (GRS) in an additional 137,559 individuals of diverse ancestry, including 10,159 T2D cases, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned GRS are more strongly associated with coronary artery disease and end-stage diabetic nephropathy than an overall T2D GRS across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings demonstrate the value of integrating multi-ancestry GWAS with single-cell epigenomics to disentangle the aetiological heterogeneity driving the development and progression of T2D, which may offer a route to optimise global access to genetically-informed diabetes care.
1 aSuzuki, Ken1 aHatzikotoulas, Konstantinos1 aSoutham, Lorraine1 aTaylor, Henry, J1 aYin, Xianyong1 aLorenz, Kim, M1 aMandla, Ravi1 aHuerta-Chagoya, Alicia1 aRayner, Nigel, W1 aBocher, Ozvan1 ade, S, V Arruda A1 aSonehara, Kyuto1 aNamba, Shinichi1 aLee, Simon, S K1 aPreuss, Michael, H1 aPetty, Lauren, E1 aSchroeder, Philip1 aVanderwerff, Brett1 aKals, Mart1 aBragg, Fiona1 aLin, Kuang1 aGuo, Xiuqing1 aZhang, Weihua1 aYao, Jie1 aKim, Young, Jin1 aGraff, Mariaelisa1 aTakeuchi, Fumihiko1 aNano, Jana1 aLamri, Amel1 aNakatochi, Masahiro1 aMoon, Sanghoon1 aScott, Robert, A1 aCook, James, P1 aLee, Jung-Jin1 aPan, Ian1 aTaliun, Daniel1 aParra, Esteban, J1 aChai, Jin-Fang1 aBielak, Lawrence, F1 aTabara, Yasuharu1 aHai, Yang1 aThorleifsson, Gudmar1 aGrarup, Niels1 aSofer, Tamar1 aWuttke, Matthias1 aSarnowski, Chloe1 aGieger, Christian1 aNousome, Darryl1 aTrompet, Stella1 aKwak, Soo-Heon1 aLong, Jirong1 aSun, Meng1 aTong, Lin1 aChen, Wei-Min1 aNongmaithem, Suraj, S1 aNoordam, Raymond1 aJ Y Lim, Victor1 aTam, Claudia, H T1 aJoo, Yoonjung, Yoonie1 aChen, Chien-Hsiun1 aRaffield, Laura, M1 aPrins, Bram, Peter1 aNicolas, Aude1 aYanek, Lisa, R1 aChen, Guanjie1 aBrody, Jennifer, A1 aKabagambe, Edmond1 aAn, Ping1 aXiang, Anny, H1 aChoi, Hyeok, Sun1 aCade, Brian, E1 aTan, Jingyi1 aBroadaway, Alaine1 aWilliamson, Alice1 aKamali, Zoha1 aCui, Jinrui1 aAdair, Linda, S1 aAdeyemo, Adebowale1 aAguilar-Salinas, Carlos, A1 aAhluwalia, Tarunveer, S1 aAnand, Sonia, S1 aBertoni, Alain1 aBork-Jensen, Jette1 aBrandslund, Ivan1 aBuchanan, Thomas, A1 aBurant, Charles, F1 aButterworth, Adam, S1 aCanouil, Mickaël1 aChan, Juliana, C N1 aChang, Li-Ching1 aChee, Miao-Li1 aChen, Ji1 aChen, Shyh-Huei1 aChen, Yuan-Tsong1 aChen, Zhengming1 aChuang, Lee-Ming1 aCushman, Mary1 aDanesh, John1 aDas, Swapan, K1 ade Silva, Janaka1 aDedoussis, George1 aDimitrov, Latchezar1 aDoumatey, Ayo, P1 aDu, Shufa1 aDuan, Qing1 aEckardt, Kai-Uwe1 aEmery, Leslie, S1 aEvans, Daniel, S1 aEvans, Michele, K1 aFischer, Krista1 aFloyd, 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Jennifer, A1 aSo, Wing, Yee1 aStančáková, Alena1 aSteinthorsdottir, Valgerdur1 aStilp, Adrienne, M1 aStrauch, Konstantin1 aTaylor, Kent, D1 aThorand, Barbara1 aThorsteinsdottir, Unnur1 aTomlinson, Brian1 aTran, Tam, C1 aTsai, Fuu-Jen1 aTuomilehto, Jaakko1 aTusié-Luna, Teresa1 aUdler, Miriam, S1 aValladares-Salgado, Adan1 avan Dam, Rob, M1 avan Klinken, Jan, B1 aVarma, Rohit1 aWacher-Rodarte, Niels1 aWheeler, Eleanor1 aWickremasinghe, Ananda, R1 aDijk, Ko Willems1 aWitte, Daniel, R1 aYajnik, Chittaranjan, S1 aYamamoto, Ken1 aYamamoto, Kenichi1 aYoon, Kyungheon1 aYu, Canqing1 aYuan, Jian-Min1 aYusuf, Salim1 aZawistowski, Matthew1 aZhang, Liang1 aZheng, Wei1 aProject, Biobank, Japan1 aBioBank, Penn, Medicine1 aCenter, Regeneron, Genetics1 aConsortium, eMERGE1 aRaffel, Leslie, J1 aIgase, Michiya1 aIpp, Eli1 aRedline, Susan1 aCho, Yoon Shin1 aLind, Lars1 aProvince, Michael, A1 aFornage, Myriam1 aHanis, Craig, L1 aIngelsson, Erik1 aZonderman, Alan, B1 aPsaty, Bruce, M1 aWang, Ya-Xing1 aRotimi, Charles, N1 aBecker, Diane, M1 aMatsuda, Fumihiko1 aLiu, Yongmei1 aYokota, Mitsuhiro1 aKardia, Sharon, L R1 aPeyser, Patricia, A1 aPankow, James, S1 aEngert, James, C1 aBonnefond, Amélie1 aFroguel, Philippe1 aWilson, James, G1 aSheu, Wayne, H H1 aWu, Jer-Yuarn1 aHayes, Geoffrey1 aMa, Ronald, C W1 aWong, Tien-Yin1 aMook-Kanamori, Dennis, O1 aTuomi, Tiinamaija1 aChandak, Giriraj, R1 aCollins, Francis, S1 aBharadwaj, Dwaipayan1 aParé, Guillaume1 aSale, Michèle, M1 aAhsan, Habibul1 aMotala, Ayesha, A1 aShu, Xiao-Ou1 aPark, Kyong-Soo1 aJukema, Wouter1 aCruz, Miguel1 aChen, Yii-Der Ida1 aRich, Stephen, S1 aMcKean-Cowdin, Roberta1 aGrallert, Harald1 aCheng, Ching-Yu1 aGhanbari, Mohsen1 aTai, E-Shyong1 aDupuis, Josée1 aKato, Norihiro1 aLaakso, Markku1 aKöttgen, Anna1 aKoh, Woon-Puay1 aBowden, Donald, W1 aPalmer, Colin, N A1 aKooner, Jaspal, S1 aKooperberg, Charles1 aLiu, Simin1 aNorth, Kari, E1 aSaleheen, Danish1 aHansen, Torben1 aPedersen, Oluf1 aWareham, Nicholas, J1 aLee, Juyoung1 aKim, Bong-Jo1 aMillwood, Iona, Y1 aWalters, Robin, G1 aStefansson, Kari1 aGoodarzi, Mark, O1 aMohlke, Karen, L1 aLangenberg, Claudia1 aHaiman, Christopher, A1 aLoos, Ruth, J F1 aFlorez, Jose, C1 aRader, Daniel, J1 aRitchie, Marylyn, D1 aZöllner, Sebastian1 aMägi, Reedik1 aDenny, Joshua, C1 aYamauchi, Toshimasa1 aKadowaki, Takashi1 aChambers, John, C1 aC Y Ng, Maggie1 aSim, Xueling1 aBelow, Jennifer, E1 aTsao, Philip, S1 aChang, Kyong-Mi1 aMcCarthy, Mark, I1 aMeigs, James, B1 aMahajan, Anubha1 aSpracklen, Cassandra, N1 aMercader, Josep, M1 aBoehnke, Michael1 aRotter, Jerome, I1 aVujkovic, Marijana1 aVoight, Benjamin, F1 aMorris, Andrew, P1 aZeggini, Eleftheria1 aVA Million Veteran Program, AMED GRIFIN Diabetes Initiative Japan1 aInternational Consortium for Blood Pressure (ICBP)1 aMeta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) uhttps://chs-nhlbi.org/node/938514002nas a2204477 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2024 eng d a1476-468700aGenetic drivers of heterogeneity in type 2 diabetes pathophysiology.0 aGenetic drivers of heterogeneity in type 2 diabetes pathophysiol c2024 Feb 193 aType 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.
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aNongmaithem, Suraj, S1 aNoordam, Raymond1 aJ Y Lim, Victor1 aTam, Claudia, H T1 aJoo, Yoonjung, Yoonie1 aChen, Chien-Hsiun1 aRaffield, Laura, M1 aPrins, Bram, Peter1 aNicolas, Aude1 aYanek, Lisa, R1 aChen, Guanjie1 aBrody, Jennifer, A1 aKabagambe, Edmond1 aAn, Ping1 aXiang, Anny, H1 aChoi, Hyeok, Sun1 aCade, Brian, E1 aTan, Jingyi1 aBroadaway, Alaine1 aWilliamson, Alice1 aKamali, Zoha1 aCui, Jinrui1 aThangam, Manonanthini1 aAdair, Linda, S1 aAdeyemo, Adebowale1 aAguilar-Salinas, Carlos, A1 aAhluwalia, Tarunveer, S1 aAnand, Sonia, S1 aBertoni, Alain1 aBork-Jensen, Jette1 aBrandslund, Ivan1 aBuchanan, Thomas, A1 aBurant, Charles, F1 aButterworth, Adam, S1 aCanouil, Mickaël1 aChan, Juliana, C N1 aChang, Li-Ching1 aChee, Miao-Li1 aChen, Ji1 aChen, Shyh-Huei1 aChen, Yuan-Tsong1 aChen, Zhengming1 aChuang, Lee-Ming1 aCushman, Mary1 aDanesh, John1 aDas, Swapan, K1 ade Silva, Janaka1 aDedoussis, George1 aDimitrov, Latchezar1 aDoumatey, Ayo, P1 aDu, Shufa1 aDuan, Qing1 aEckardt, Kai-Uwe1 aEmery, Leslie, S1 aEvans, Daniel, S1 aEvans, Michele, K1 aFischer, Krista1 aFloyd, James, S1 aFord, Ian1 aFranco, Oscar, H1 aFrayling, Timothy, M1 aFreedman, Barry, I1 aGenter, Pauline1 aGerstein, Hertzel, C1 aGiedraitis, Vilmantas1 aGonzález-Villalpando, Clicerio1 aGonzalez-Villalpando, Maria, Elena1 aGordon-Larsen, Penny1 aGross, Myron1 aGuare, Lindsay, A1 aHackinger, Sophie1 aHakaste, Liisa1 aHan, Sohee1 aHattersley, Andrew, T1 aHerder, Christian1 aHorikoshi, Momoko1 aHoward, Annie-Green1 aHsueh, Willa1 aHuang, Mengna1 aHuang, Wei1 aHung, Yi-Jen1 aHwang, Mi, Yeong1 aHwu, Chii-Min1 aIchihara, Sahoko1 aIkram, Mohammad, Arfan1 aIngelsson, Martin1 aIslam, Md, Tariqul1 aIsono, Masato1 aJang, Hye-Mi1 aJasmine, Farzana1 aJiang, Guozhi1 aJonas, Jost, B1 aJørgensen, Torben1 aKamanu, Frederick, K1 aKandeel, Fouad, R1 aKasturiratne, Anuradhani1 aKatsuya, Tomohiro1 aKaur, Varinderpal1 aKawaguchi, Takahisa1 aKeaton, Jacob, M1 aKho, Abel, N1 aKhor, Chiea-Chuen1 aKibriya, Muhammad, G1 aKim, 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Kevin1 aSankareswaran, Alagu1 aSattar, Naveed1 aSchönherr, Sebastian1 aShahriar, Mohammad1 aShen, Botong1 aShi, Jinxiu1 aShin, Dong, Mun1 aShojima, Nobuhiro1 aSmith, Jennifer, A1 aSo, Wing, Yee1 aStančáková, Alena1 aSteinthorsdottir, Valgerdur1 aStilp, Adrienne, M1 aStrauch, Konstantin1 aTaylor, Kent, D1 aThorand, Barbara1 aThorsteinsdottir, Unnur1 aTomlinson, Brian1 aTran, Tam, C1 aTsai, Fuu-Jen1 aTuomilehto, Jaakko1 aTusié-Luna, Teresa1 aUdler, Miriam, S1 aValladares-Salgado, Adan1 avan Dam, Rob, M1 avan Klinken, Jan, B1 aVarma, Rohit1 aWacher-Rodarte, Niels1 aWheeler, Eleanor1 aWickremasinghe, Ananda, R1 aDijk, Ko Willems1 aWitte, Daniel, R1 aYajnik, Chittaranjan, S1 aYamamoto, Ken1 aYamamoto, Kenichi1 aYoon, Kyungheon1 aYu, Canqing1 aYuan, Jian-Min1 aYusuf, Salim1 aZawistowski, Matthew1 aZhang, Liang1 aZheng, Wei1 aRaffel, Leslie, J1 aIgase, Michiya1 aIpp, Eli1 aRedline, Susan1 aCho, Yoon Shin1 aLind, Lars1 aProvince, Michael, A1 aFornage, Myriam1 aHanis, Craig, L1 aIngelsson, Erik1 aZonderman, Alan, B1 aPsaty, Bruce, M1 aWang, Ya-Xing1 aRotimi, Charles, N1 aBecker, Diane, M1 aMatsuda, Fumihiko1 aLiu, Yongmei1 aYokota, Mitsuhiro1 aKardia, Sharon, L R1 aPeyser, Patricia, A1 aPankow, James, S1 aEngert, James, C1 aBonnefond, Amélie1 aFroguel, Philippe1 aWilson, James, G1 aSheu, Wayne, H H1 aWu, Jer-Yuarn1 aHayes, Geoffrey1 aMa, Ronald, C W1 aWong, Tien-Yin1 aMook-Kanamori, Dennis, O1 aTuomi, Tiinamaija1 aChandak, Giriraj, R1 aCollins, Francis, S1 aBharadwaj, Dwaipayan1 aParé, Guillaume1 aSale, Michèle, M1 aAhsan, Habibul1 aMotala, Ayesha, A1 aShu, Xiao-Ou1 aPark, Kyong-Soo1 aJukema, Wouter1 aCruz, Miguel1 aChen, Yii-Der Ida1 aRich, Stephen, S1 aMcKean-Cowdin, Roberta1 aGrallert, Harald1 aCheng, Ching-Yu1 aGhanbari, Mohsen1 aTai, E-Shyong1 aDupuis, Josée1 aKato, Norihiro1 aLaakso, Markku1 aKöttgen, Anna1 aKoh, Woon-Puay1 aBowden, Donald, W1 aPalmer, Colin, N A1 aKooner, Jaspal, S1 aKooperberg, Charles1 aLiu, Simin1 aNorth, Kari, E1 aSaleheen, Danish1 aHansen, Torben1 aPedersen, Oluf1 aWareham, Nicholas, J1 aLee, Juyoung1 aKim, Bong-Jo1 aMillwood, Iona, Y1 aWalters, Robin, G1 aStefansson, Kari1 aAhlqvist, Emma1 aGoodarzi, Mark, O1 aMohlke, Karen, L1 aLangenberg, Claudia1 aHaiman, Christopher, A1 aLoos, Ruth, J F1 aFlorez, Jose, C1 aRader, Daniel, J1 aRitchie, Marylyn, D1 aZöllner, Sebastian1 aMägi, Reedik1 aMarston, Nicholas, A1 aRuff, Christian, T1 avan Heel, David, A1 aFiner, Sarah1 aDenny, Joshua, C1 aYamauchi, Toshimasa1 aKadowaki, Takashi1 aChambers, John, C1 aC Y Ng, Maggie1 aSim, Xueling1 aBelow, Jennifer, E1 aTsao, Philip, S1 aChang, Kyong-Mi1 aMcCarthy, Mark, I1 aMeigs, James, B1 aMahajan, Anubha1 aSpracklen, Cassandra, N1 aMercader, Josep, M1 aBoehnke, Michael1 aRotter, Jerome, I1 aVujkovic, Marijana1 aVoight, Benjamin, F1 aMorris, Andrew, P1 aZeggini, Eleftheria1 aVA Million Veteran Program uhttps://chs-nhlbi.org/node/9619